A novel recessive mutation in OXR1 is identified in patient with hearing loss recapitulated by the knockdown zebrafish.

Hereditary hearing loss is a highly genetically heterogeneous disorder. More than 150 genes have been identified to link to human non-syndromic hearing impairment. To identify genetic mutations and underlying molecular mechanisms in affected individuals and families with congenital hearing loss, we recruited a cohort of 389 affected individuals in 354 families for whole-exome sequencing analysis. In this study, we report a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in the OXR1 gene, which was identified in a 4-year-old girl with sensorineural hearing loss. OXR1 encodes Oxidation Resistance 1 and is evolutionarily conserved from zebrafish to human. We found that the ortholog oxr1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL) in zebrafish. Knockdown of oxr1b in zebrafish resulted in a significant developmental defect of SAG and pLL. This phenotype can be rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs. OXR1-associated pathway analysis revealed that mutations of TBC1D24, a TLDc-domain-containing homolog gene of OXR1, have previously been identified in patients with hearing loss. Interestingly, mutations or knockout of OXR1 interacting molecules such as ATP6V1B1 and ESR1 are also associated with hearing loss in patients or animal models, hinting an important role of OXR1 and associated partners in cochlear development and hearing function.

Epidemiological behaviour and interventions of malaria in Niger, 2010-2019: a time-series analysis of national surveillance data.

BACKGROUND: Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. METHODS: A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. RESULTS: Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10-24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. CONCLUSIONS: The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Genomic Characteristics of Emerging Intraerythrocytic Anaplasma capra and High Prevalence in Goats, China.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

Albumin-to-globulin ratio (AGR) as a potential marker of predicting lupus nephritis in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To evaluate a potential role of albumin-to-globulin ratio (AGR) in the development of lupus nephritis (LN) and determine the potential to use AGR as a marker for future LN in systemic lupus erythematosus (SLE) patients. METHODS: 194 newly diagnosed SLE patients without renal impairment were followed. The clinical data were collected and analyzed at the time of initial diagnosis of SLE and the end of follow-up. We compared baseline characteristics between those who did or did not develop LN on follow-up. Univariate and multivariate Cox hazard analysis were used to identify predictors of lupus nephritis. RESULTS: Among the 194 newly diagnosed SLE patients without renal impairment, 26 (13.40%) patients were diagnosed with LN during a median follow-up of 53.87 months. On univariate Cox analysis, patients with the history of alopecia, higher SBP, lower AGR, lower CRP, lower C3, lower C4, higher anti-dsDNA Ab, presence of ANA homogeneous patterns or higher SLEDAI had an increased probability of developing LN. In a multivariate model, the history of alopecia (adjust hazard ratio, aHR = 3.614, 95%CI 1.365-9.571 P = 0.010), lower AGR (aHR = 6.968, 95%CI 1.873-25.919, P = 0.004), lower CRP (aHR = 4.230, 95%CI 1.591-11.247, P = 0.004) and higher level of anti-dsDNA (aHR = 2.675, 95%CI 1.008-7.093, P = 0.048) were independently associated with an increased risk of developing LN after adjusting for covariates. CONCLUSION: Our findings indicated that SLE patients with low AGR, low CRP, high anti-dsDNA and the history of alopecia were more likely to develop LN in the course of SLE. AGR shown the greatest hazard for developing LN among them, it may be a strong predictor.

Trial marriage model-Female mate choice under male interference.

In sexually reproducing animals, the process of mate choice by females is often mixed with the process of male-male competition. Current models of female male choice focus mainly on how females identify the higher quality of males, but neglect the effect of male-male competition on the mate choice of females. Therefore, it remains controversial what is the relative importance of two processes in forming a social bond. We propose a new 'trial marriage' model for females' mate choice. The model assumes that females unconditionally accept any male they first encounter as their mating partner, and then conditionally switch mates to a new male of higher quality than their current partner when male-male competition occurs. This model was tested in the green weevil Hypomeces squamosus by exploring how females switched mates when males' mating interference was experimentally induced. The likelihood that females switched mates, as well as their conditional acceptance criteria of a new mate, was both raised with the intensity of males' mating interference that was manipulated in an enhanced encounter rate experiment, and in male introduction or stepwise removal experiments. These experimental findings confirm that a 'trial marriage' strategy occurs during females' mate choice. Compared with other strategies, it is more beneficial for females to choose a better mate without paying the costs of identifying males as suggested by the 'trial marriage' strategy. More importantly, using the current partner quality as the conditional acceptance threshold of new mates, females can choose better males in future encounters with potential mates. In the green weevils, males' preference for larger females and the higher possibility of the largest male winning an interference are mixed together when males' mating interference reaches a higher intensity. Therefore, the consequence of a male interference will determine which male could be chosen by a female. Under this condition, conditional acceptance of the winner becomes the most beneficial strategy of females in choosing their mates. We thus suggest that the 'trial marriage' strategy would be more efficient when males' mating interference becomes the determinant factor of females' mate choice.

First Report of Southern Blight of Manglietia decidua Caused by Sclerotium rolfsii in China.

Manglietia decidua, named 'Hua manglietia', belonging to the Magnoliaceae family, is one of the most important ornamental plant in China. In 2019 and 2020, an unknown disease caused 3- to 12-month plants of M. decidua to wither and die in the field in Zhanjiang, Guangdong province（N21°9'3";E110°17'47"）. Initially, the infected plants showed leaves dehydration, chlorosis and wilting with water-soaked lesions on stems at ground level. About 7 days later, the plants completely wilted, collapsed and died. Delayed and stunted growth with wilting of foliage continued through the whole year. Dense white mycelial mat and small white-to-brown spherical sclerotia were observed on the surface of the stalk lesion when weather conditions were warm and humid. Approximately 10% of plants were infected. Especially from July to October 2020, up to 30% of about 500 plants were infected and died. To identify the causal agents of the disease, infected tissue and sclerotia were collected, surface disinfected in 75% alcohol for 30s and 30% hydrogen peroxide solution for 5 min, and washed with sterile water for 1 min. The surface disinfected tissue and sclerotia were put on potato dextrose agar containing ampicillin (50mg/L) and kept in an incubator at 25°C in the dark. Fast growing fungus colonies with white mycelium and numerous sclerotia developed in the plates after 6 to 8 days of incubation. The hyphae were septate, hyaline and formed typically clamp connection after 10 days of growth. Sclerotia were initially white and became tan to dark brown over time and 1.0 to 3.0 mm (2.13 mm on average, n=124) in diameter at maturity. For molecular identification，the ITS region was amplified using primer pair ITS1/ITS4 (White et al. 1990). A 666 bp PCR product was sequenced (GenBank accession no. MW093622) and shared above 99% sequence identity with some Athelia rolfsii isolates (GenBank accession Nos. HQ895869, KX499470 and AB075290). Based on morphological and molecular characteristics, the fungus was identified as Sclerotium rolfsii (teleomorph A. rolfsii) （Paul et al. 2017，Xu et al. 2010. Pathogenicity tests were conducted by inoculating ten healthy 1-year-old M. decidua plants grown in pots. Five sclerotia and mycelial mat obtained from 15-day-old cultures were buried adjacent to the stem of each unwounded healthy plant. Non-inoculated plants served as controls. After inoculation, the plants were maintained in a 25-28 ℃ greenhouse and watered regularly to keep the soil moisture content at about 15%. Symptoms of southern blight were observed on all inoculated plants, which began to wilt 7 to 10 days after inoculation and died within 15 to 20 days. The control plants remained healthy. S. rolfsii was again isolated from the artificially inoculated plants, but not from non-inoculated plants. The pathogenicity test was repeated twice and the results were the same. S. rolfsii has an extensive host range worldwide and the common host ornamental plants are Iris, Chrysanthemum, CymbidiumTrifolium, Jasminum, Begonia, and Stevia etc. in China. To our knowledge, this is the first report of southern blight caused by S. rolfsiii on M. decidua in China. M. decidua is a horticultural plant which belongs to the protected and endangered tree species. This finding is important to alert growers to realize the proper management of this disease during species protection and cultivar extension.

High-power 266 nm laser generation with a NaSr3Be3B3O9F4 crystal.

We demonstrate a 266 nm ultraviolet (UV) picosecond laser by fourth-harmonic generation of a Nd:YAG laser with a 5.4 mm thick NaSr3Be3B3O9F4 (NSBBF) crystal. A maximum output power exceeding 1 W at 266 nm was obtained (the highest output power being 1.6 W), corresponding to a conversion efficiency of 10.3%. The stability measurements on the NSBBF crystal with a fluctuation of 3.34% at 200 mW within 1 h indicate that it is a promising UV nonlinear optical material for practical applications. In addition, for the first time, to the best of our knowledge, we measured the effective nonlinear coefficient of NSBBF crystal at 266 nm and compared it with that of ß-BaB2O4 crystal.

High-energy single-frequency 167 nm deep-ultraviolet laser.

We report a high-energy single-frequency deep-ultraviolet (DUV) solid-state laser at 167.079 nm by the eighth-harmonic generation of a diode-pumped Nd:LGGG laser. A maximum DUV laser output energy of 1.5 µJ at a 5 Hz repetition rate with a 200 µs pulse duration is achieved. The central wavelength of the DUV laser is located at 167.079 nm and can be finely tuned from 167.075 to 167.083 nm. The linewidth is estimated to be 0.025 pm. To the best of our knowledge, this is the first Letter reporting a high-energy single-frequency solid-state DUV laser below 170 nm. The successful demonstration of the high-energy single-frequency DUV laser source with the unique wavelength is useful for direct detection of a Al+27 ion via resonance fluorescence in a multi-ion optical clock.

Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti-Proliferative Activity on HSC-T6 Cells.

Five previously undescribed triterpenoid saponins (1-5), along with eight known ones (6-13), were isolated from the whole plants of Anemone rivularis var. flore-minore. Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins (3 and 12) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13, which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC50 values of 18.21 and 15.56 µM, respectively.

δ Subunit-containing GABAA receptor prevents overgeneralization of fear in adult mice.

The role of δ subunit-containing GABAA receptor (GABAA(δ)R) in fear generalization is uncertain. Here, by using mice with or without genetic deletion of GABAA(δ)R and using protocols in which the conditioned tone stimuli were cross presented with different nonconditioned stimuli, we observed that when the two tone stimuli were largely similar, both genotypes froze similarly to either of them. However, when they differed markedly, the knockout mice froze much more than their wild-type littermates to the nonconditioned but not conditioned stimuli. Thus, GABAA(δ)R may prevent inappropriate fear generalization when the incoming stimuli differ clearly from the learned threat.

High-efficiency UV generation at 266 nm in a new nonlinear optical crystal NaSr3Be3B3O9F4.

266 nm laser output in NaSr3Be3B3O9F4 crystal by the fourth harmonic generation process with a picosecond mode-locked Nd-based YAG laser has been done for the first time. When the input pumping energy was 870 µJ at 532 nm, a 280 µJ 266 nm UV laser was obtained and the corresponding conversion efficiency was 35.9%. Further investigations identified that NaSr3Be3B3O9F4 has a large acceptance angle width of 0.47 (mrad • cm), a small walk-off angle of 35.43 mrad and a large deff as 0.62 pm/V for the fourth harmonic generation. These results indicate that NSBBF is applicable for high-power 266 nm laser generation.

Comparative Mitogenomic Analysis of Species Representing Six Subfamilies in the Family Tenebrionidae.

To better understand the architecture and evolution of the mitochondrial genome (mitogenome), mitogenomes of ten specimens representing six subfamilies in Tenebrionidae were selected, and comparative analysis of these mitogenomes was carried out in this study. Ten mitogenomes in this family share a similar gene composition, gene order, nucleotide composition, and codon usage. In addition, our results show that nucleotide bias was strongly influenced by the preference of codon usage for A/T rich codons which significantly correlated with the G + C content of protein coding genes (PCGs). Evolutionary rate analyses reveal that all PCGs have been subjected to a purifying selection, whereas 13 PCGs displayed different evolution rates, among which ATPase subunit 8 (ATP8) showed the highest evolutionary rate. We inferred the secondary structure for all RNA genes of Tenebrio molitor (Te2) and used this as the basis for comparison with the same genes from other Tenebrionidae mitogenomes. Some conserved helices (stems) and loops of RNA structures were found in different domains of ribosomal RNAs (rRNAs) and the cloverleaf structure of transfer RNAs (tRNAs). With regard to the AT-rich region, we analyzed tandem repeat sequences located in this region and identified some essential elements including T stretches, the consensus motif at the flanking regions of T stretch, and the secondary structure formed by the motif at the 3' end of T stretch in major strand, which are highly conserved in these species. Furthermore, phylogenetic analyses using mitogenomic data strongly support the relationships among six subfamilies: ((Tenebrionidae incertae sedis + (Diaperinae + Tenebrioninae)) + (Pimeliinae + Lagriinae)), which is consistent with phylogenetic results based on morphological traits.

167.75-nm vacuum-ultraviolet ps laser by eighth-harmonic generation of a 1342-nm Nd:YVO4 amplifier in KBBF.

We demonstrate a ps 167.75-nm vacuum-ultraviolet (VUV) laser by cascaded second-harmonic generation (SHG). The VUV laser is produced by eighth-harmonic generation (EHG) of a mode-locked ps 1342-nm Nd:YVO4 amplifier through three stages cascaded SHG with two LiB3O5 crystals and one KBe2BO3F2 crystal, successively. The 167.75-nm laser provides up to 65-µW output power, and the corresponding photon flux and photon flux density are 5.5×10(13) s(-1) and 1.6×10(18) s(-1)·cm(-2), respectively.

A novel pregnane-type alkaloid from Pachysandra terminalis inhibits methicillin-resistant Staphylococcus aureus in vitro and in vivo.

A new kind of pregnane-type alkaloid, 20α-dimethylamino-3ß-senecioylamino-16ß-hydroxy-pregn-5-ene (K-6), was isolated from Pachysandra terminalis Sieb. et Zucc., and its antibacterial activity against MRSA and MRSE was evaluated. We found that K-6 showed antibacterial effects against MRSA and MRSE with minimum inhibitory concentration values (25 mg/L), but did not induce antibiotic resistance in bacteria easily. The administration of K-6 dose-dependently improved the animal survival rate of mice infected with MRSA, with survival rates of 36.34% and 66.67% in the low-dose and high-dose groups, respectively. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. Scanning and transmission electron microscopy analyses indicated that the cytoplasm shrink of bacterial cells led to noticeable gaps between the cell membrane and cell cytoplasm, and the severely damaged cell membrane resulted in leakage of intracellular content, which ultimately caused the lethal effect of K-6 on bacteria. These findings demonstrated that K-6 is a potential agent against MRSA and MRSE.

Two new triterpenoid saponins from the aerial parts of Anemone taipaiensis.

Phytochemical study on the aerial parts of Anemone taipaiensis for the first time led to the isolation of two new oleanane-type triterpenoid saponins 1 and 2, together with four known saponins (3-6). Their structures were elucidated by extensive spectroscopic analysis and chemical evidences. Saponins 2-4 exhibited cytotoxicity against human glioblastoma U251MG cell line with IC50 values ranging from 1.56 to 80.62 µM.

Interferon-alpha and interferon-gamma modulate Fas-mediated apoptosis in mitomycin-C-resistant human Tenon's fibroblasts.

BACKGROUND: The aim of the study was to investigate, using a native mitomycin-C-resistant human Tenon's fibroblast cell line, the possibility that interferon-alpha and gamma could be used with Fas agonists as an alternative anti-fibrotic strategy to mitomycin-C in trabeculectomy. METHODS: A clinically resistant and in vitro verified mitomycin-C-resistant human Tenon's fibroblast cell line was pretreated with interferon-alpha and interferon-gamma for 48 h before stimulation with an agonistic Fas antibody (CH11) for 2 days to induce cell death. Cell death assays were undertaken. Changes in apoptosis-related proteins were determined by flow cytometry and Western blot. RESULTS: Pretreatment with interferon-alpha or interferon-gamma for 48 h increased Fas, Fas-associated protein with death domain and caspase-8 expression. Protein expression was further increased by combined exposure to interferon-alpha and gamma. Pretreatment with cytokines had no effect on Fas-L and Bcl-2. Interferon-alpha alone did not change the rate of induced cell death. A combination of interferon-alpha and gamma synergistically increased the sensitivity of mitomycin-C-resistant human Tenon's fibroblast cell line to induced cell death. An antagonistic anti-Fas antibody (ZB4) completely blocked induced cell death. Broad caspase inhibitors specific for caspases-8 and -3 reduced induced deaths in interferon pretreated mitomycin-C-resistant human Tenon's fibroblast cell line in a dose-dependent manner. CONCLUSIONS: Interferon-alpha and interferon-gamma render mitomycin-C-resistant human Tenon's fibroblast cell line sensitive to Fas-mediated apoptosis. The mechanism involves increased death-inducing signalling complex formation by upregulation of Fas, Fas-associated protein with death domain and caspase-8 expression.

Proteomic analysis of the effect of diclazuril on second-generation merozoites of Eimeria tenella.

Diclazuril has long been used as an effective benzeneacetonitrile anticoccidial for the control of Eimeria tenella that causes coccidiosis. However, the molecular mechanism underlying the anticoccidial effects of diclazuril remains elusive. In this study, a proteomic analysis of the effect of diclazuril on second-generation merozoites of E. tenella was performed. Using two-dimensional gel electrophoresis and real-time quantitative polymerase chain reaction (RT-PCR), 13 target proteins were found to be significantly affected by diclazuril treatment, with 11 of these proteins being identified as annotated proteins from E. tenella or other Apicomplexa parasites. These proteins contribute to various functions, including metabolism, protein synthesis, and host cell invasion. Using RT-PCR, we identified the potential pattern of transcriptional regulation induced by diclazuril, and we suggest some promising targets for the intervention of E. tenella infection.

An integrated data analysis reveals distribution, hosts, and pathogen diversity of Haemaphysalis concinna.

BACKGROUND: Haemaphysalis concinna, carrying multiple pathogens, has attracted increasing attention because of its expanded geographical range and significant role in disease transmission. This study aimed to identify the potential public health risks posed by H. concinna and H. concinna-associated pathogens. METHODS: A comprehensive database integrating a field survey, literature review, reference book, and relevant websites was developed. The geographical distribution of H. concinna and its associated pathogens was illustrated using ArcGIS. Meta-analysis was performed to estimate the prevalence of H. concinna-associated microbes. Phylogenetic and geographical methods were used to investigate the role of birds in the transmission of H. concinna-associated microbes. The potential global distribution of H. concinna was predicted by ecological niche modeling. RESULTS: Haemaphysalis concinna was distributed in 34 countries across the Eurasian continent, predominantly in China, Russia, and Central Europe. The tick species carried at least 40 human pathogens, including six species in the Anaplasmataceae family, five species of Babesia, four genospecies in the complex Borrelia burgdorferi sensu lato, ten species of spotted fever group rickettsiae, ten species of viruses, as well as Francisella, Coxiella, and other bacteria. Haemaphysalis concinna could parasitize 119 host species, with nearly half of them being birds, which played a crucial role in the long-distance transmission of tick-borne microbes. Our predictive modeling suggested that H. concinna could potentially survive in regions where the tick has never been previously recorded such as central North America, southern South America, southeast Oceania, and southern Africa. CONCLUSIONS: Our study revealed the wide distribution, broad host range, and pathogen diversity of H. concinna. Authorities, healthcare professionals, and the entire community should address the growing threat of H. concinna and associated pathogens. Tick monitoring and control, pathogen identification, diagnostic tools, and continuous research should be enhanced.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Virome diversity shaped by genetic evolution and ecological landscape of Haemaphysalis longicornis.

BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.